HDX-MS guided drug discovery: small molecules and biopharmaceuticals
HDX-MS guided drug discovery: small molecules and biopharmaceuticals
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DOI：
10.1016/j.sbi.2014.08.007
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发表时间：
2014-10-01
影响因子：
6.8
通讯作者：
Griffin, Patrick R.
中科院分区：
文献类型：
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作者：
Marciano, David P.;Dharmarajan, Venkatasubramanian;Griffin, Patrick R.
氢/氘交换与质谱（HDX-MS 或 DXMS）相结合已成为开发小分子疗法和生物制药的重要工具。这些进步的核心是自动化 HDX-MS 平台和软件的改进，可以快速采集和处理实验数据。将大量配体的 HDX-MS 谱与其功能输出关联起来，可以开发结构活性关系 (SAR) 并根据功能选择性描述配体类别。 HDX-MS 还被应用于解决生物制药不断涌现带来的许多独特挑战。在这里，我们回顾了 HDX-MS 在药物发现中的最新应用、技术和软件的最新进展，并提供了对未来前景的展望。
Hydrogen/deuterium exchange coupled with mass spectrometry (HDX-MS or DXMS) has emerged as an important tool for the development of small molecule therapeutics and biopharmaceuticals. Central to these advances have been improvements to automated HDX-MS platforms and software that allow for the rapid acquisition and processing of experimental data. Correlating the HDX-MS profile of large numbers of ligands with their functional outputs has enabled the development of structure activity relationships (SAR) and delineation of ligand classes based on functional selectivity. HDX-MS has also been applied to address many of the unique challenges posed by the continued emergence of biopharmaceuticals. Here we review the latest applications of HDX-MS to drug discovery, recent advances in technology and software, and provide perspective on future outlook.